Identification of the cell lineage at the origin of basal cell carcinoma.

Abstract	For most types of cancers, the cell at the origin of tumour initiation is still unknown. Here, we used mouse genetics to identify cells at the origin of basal cell carcinoma (BCC), which is one of the most frequently occurring types of cancer in humans, and can result from the activation of the Hedgehog signalling pathway. Using mice conditionally expressing constitutively active Smoothened mutant (SmoM2), we activated Hedgehog signalling in different cellular compartments of the skin epidermis and determined in which compartments Hedgehog activation induces BCC formation. Activation of SmoM2 in hair follicle bulge stem cells and their transient amplifying progenies did not induce cancer formation, demonstrating that BCC does not originate from bulge stem cells, as previously thought. Using clonal analysis, we found that BCC arises from long-term resident progenitor cells of the interfollicular epidermis and the upper infundibulum. Our studies uncover the cells at the origin of BCC in mice and demonstrate that expression of differentiation markers in tumour cells is not necessarily predictive of the cancer initiating cells.
Authors	Khalil Kass Youssef, Alexandra Van Keymeulen, Gäelle Lapouge, Benjamin Beck, Cindy Michaux, Younes Achouri, Panagiota A Sotiropoulou, Cédric Blanpain
Journal	Nature cell biology (Nat Cell Biol) Vol. 12 Issue 3 Pg. 299-305 (Mar 2010) ISSN: 1476-4679 [Electronic] England
PMID	20154679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Bacterial Proteins Cadherins Gt(ROSA)26Sor non-coding RNA, mouse Hedgehog Proteins Integrin beta4 Keratin-14 Keratin-15 Keratin-19 Krt10 protein, mouse Krt14 protein, mouse Krt15 protein, mouse Kruppel-Like Transcription Factors Luminescent Proteins Patched Receptors Proteins RNA, Untranslated Receptors, Cell Surface Receptors, G-Protein-Coupled Shh protein, mouse Smo protein, mouse Smoothened Receptor yellow fluorescent protein, Bacteria Keratin-10 Cre recombinase Integrases
Topics	Animals Bacterial Proteins (genetics, metabolism) Cadherins (metabolism) Carcinoma, Basal Cell (metabolism, pathology) Cell Count Cell Differentiation Cell Lineage Clone Cells (metabolism, pathology) Ear, External (pathology) Epidermis (metabolism, pathology) Epithelial Cells (metabolism, pathology) Genes, Reporter (genetics) Hair Follicle (metabolism, pathology) Hedgehog Proteins (genetics) Integrases (genetics) Integrin beta4 (metabolism) Keratin-10 (metabolism) Keratin-14 (genetics) Keratin-15 (genetics, metabolism) Keratin-19 (genetics) Kruppel-Like Transcription Factors (metabolism) Luminescent Proteins (genetics, metabolism) Mice Mice, Inbred Strains Mice, Transgenic Models, Biological Neoplastic Stem Cells (metabolism, pathology) Patched Receptors Proteins (genetics, metabolism) RNA, Untranslated Receptors, Cell Surface (metabolism) Receptors, G-Protein-Coupled (genetics, metabolism) Skin (metabolism, pathology) Smoothened Receptor Tail (pathology)

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